Two distinct members of the S2 serine protease subfamily have been previously identified in humans. One is protein L56/PRSS11 (Zumbrunn et al., (1996), FEBS Lett. 398:187–192; Genbank Protein ID: CAA69226). The other is protein Omi/HtrA2 (Faccio et al., (2000), J. Biol. Chem. 275:2581–2588, Genbank Protein ID: AAB94569). These proteases share homologues with a bacterial HtrA (high-temperature requirement A) endoprotease, which acts as a chaperone at low temperatures and as a proteolytic enzyme that removes denatured or damaged substrates at elevated temperatures. The two members of human S2 serine proteases share extensive homology at their carboxy termini.
Human S2 serine proteases are believed to play important roles in cellular physiology. PRSS11 is upregulated in osteoarthritic cartilage and secreted. It was suggested that PRSS11 regulates the availability of IGFs by cleaving IGF-binding proteins. HtrA2 is upregulated during stress and appears to localize in the endoplasmic reticulum. It was shown that HtrA2 regulates apoptosis by interacting with the X chromosome-linked inhibitor of apoptosis (XIAP) (Suzuki et al., (2001), Mol cell 8:613–21).